GANAB and N-Glycans Substrates Are Relevant in Human Physiology,Polycystic Pathology and Multiple Sclerosis: A Review

Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident N-glycans participate with the Glc₃Man₉GlcNAc₂ highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio. However, under abnormal conditions, the cell adapts to the glucose availability by adopting an aerobic or anaerobic regimen of glycolysis, or to external stimuli through internal or external recognition patterns, so it responds to pathogenic noxa with unfolded protein response (UPR). UPR can affect Multiple Sclerosis (MS) and several neurological and metabolic diseases via the BiP stress sensor, resulting in ATF6, PERK and IRE1 activation. Furthermore, the abnormal GANAB expression has been observed in MS, systemic lupus erythematous, male germinal epithelium and predisposed highly replicating cells of the kidney tubules and bile ducts. The latter is the case of Polycystic Liver Disease (PCLD) and Polycystic Kidney Disease (PCKD), where genetically induced GANAB loss affects polycystin-1 (PC1) and polycystin-2 (PC2), resulting in altered protein quality control and cyst formation phenomenon. Our topics resume the role of glycans in cell physiology, highlighting the N-glycans one, as a substrate of GANAB, which is an emerging key molecule in MS and other human pathologies.     

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.     

Retrieval of leaf area index in different vegetation types using high resolution satellite data

With the successful launch of the IKONOS satellite, very high geometric resolution imagery is within reach of civilian users. In the 1-m spatial resolution images acquired by the IKONOS satellite, details of buildings, individual trees, and vegetation structural variations are detectable. The visibility of such details opens up many new applications, which require the use of geometrical information contained in the images. This paper presents an application in which spectral and textural information is used for mapping the leaf area index (LAI) of different vegetation types. This study includes the estimation of LAI by different spectral vegetation indices (SVIs) combined with image textural information and geostatistical parameters derived from high resolution satellite data. It is shown that the relationships between spectral vegetation indices and biophysical parameters should be developed separately for each vegetation type, and that the combination of the texture indices and vegetation indices results in an improved fit of the regression equation for most vegetation types when compared with one derived from SVIs alone. High within-field spatial variability was found in LAI, suggesting that high resolution mapping of LAI may be relevant to the introduction of precision farming techniques in the agricultural management strategies of the investigated area.     

Solving the electricity production planning problem by a column generation based heuristic

This paper presents a heuristic method based on column generation for the EDF (Electricité De France) long-term electricity production planning problem proposed as subject of the ROADEF/EURO 2010 Challenge. This is to our knowledge the first-ranked method among those methods based on mathematical programming, and was ranked fourth overall. The problem consists in determining a production plan over the whole time horizon for each thermal power plant of the French electricity company, and for nuclear plants, a schedule of plant outages which are necessary for refueling and maintenance operations. The average cost of the overall outage and production planning, computed over a set of demand scenarios, is to be minimized. The method proceeds in two stages. In the first stage, dates for outages are fixed once for all for each nuclear plant. Data are aggregated with a single average scenario and reduced time steps, and a set-partitioning reformulation of this aggregated problem is solved for fixing outage dates with a heuristic based on column generation. The pricing problem associated with each nuclear plant is a shortest path problem in an appropriately constructed graph. In the second stage, the reload level is determined at each date of an outage, considering now all scenarios. Finally, the production quantities between two outages are optimized for each plant and each scenario by solving independent linear programming problems.     

Improving Scalability of Application-Level Checkpoint-Recovery by Reducing Checkpoint Sizes

The execution times of large-scale parallel applications on nowadays multi/many-core systems are usually longer than the mean time between failures. Therefore, parallel applications must tolerate hardware failures to ensure that not all computation done is lost on machine failures. Checkpointing and rollback recovery is one of the most popular techniques to implement fault-tolerant applications. However, checkpointing parallel applications is expensive in terms of computing time, network utilization and storage resources. Thus, current checkpoint-recovery techniques should minimize these costs in order to be useful for large scale systems. In this paper three different and complementary techniques to reduce the size of the checkpoints generated by application-level checkpointing are proposed and implemented. Detailed experimental results obtained on a multicore cluster show the effectiveness of the proposed methods to reduce checkpointing cost.     

The Marching Intersections algorithm for merging range images

A new algorithm for the integration of partially overlapping range images into a triangular mesh is presented. The algorithm consists of three main steps: it locates the intersections between the range surfaces and a reference grid chosen by the user, then merges all nearly coincident and redundant intersections according to a proximity criterion, and, finally, reconstructs the merged surface(s) from the filtered intersection set. Compared with previous methods, which adopt a volumetric approach, our algorithm shows lower computational costs and improves the accuracy of the surfaces produced. It takes into account the quality of the input measurements and is able to patch small holes corresponding to the parts of the 3D scanned object that were not observed by the acquisition device. The algorithm has been tested on several datasets of range maps; graphical and numeric results are reported.     

Molecular Effects of Chronic Exposure to Palmitate in Intestinal Organoids: A New Model to Study Obesity and Diabetes

Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.     

A Sustainable Process for the Production of Varnishes Based on Pelargonic Acid Esters

This work demonstrates the possibility of using pelargonic acid (PA) esters as solvents for vegetable-based varnishes. First, PA was efficiently produced through a chemocatalytic cleavage of oleic acid, practicing an optimized scale-up of previously developed conditions. PA was then esterified with several alcohols ROH (R = Me, i-Pr, n-Bu, n-Hex, 2-ethylhexyl, and sec-octyl) and the products were formulated with a commercial rosin (Phenolic Modified Rosin Esters). Dynamic light scattering (DLS) measures and determination of rheological parameters of the corresponding varnishes disclosed their suitability for applications in offset, coldset, heatset printing inks, and coatings. Furthermore, inks obtained were used to efficiently produce preliminary industrial offset prints.